Accurate risk profile
Anna Østergaard: 'In order to determine the most appropriate dosage, we need to create a molecular risk profile for each child. Based on that, we can reduce or increase therapy. Despite the high chance of curing children with the ETV6::RUNX1 gene fusion, about 2% of children experience a return of the disease after their treatment, also called relapse. 'We need to know exactly how to recognize these children at an early stage. That way we can set up study protocols for therapy reduction without reducing the chance of cure.'To this end, Østergaard examined the DNA of individual leukemia cells from children with an ETV6::RUNX1 ALL relapse. She concluded that single cell analysis of the DNA makes the picture we have more complete and may ultimately help identify these children.
This insight brings closer follow-up research on possible chemotherapy reduction for these low-risk children. Less treatment may provide fewer side effects and therefore a better quality of life for these children.
International collaboration
Although this form of leukemia is the most common form of childhood cancer, the study group for this study was very small. 'In the Netherlands, we only had material from a few children from diagnosis and relapse to conduct this study.' By collaborating internationally with the U.S. pediatric oncology research hospital St. Jude, and biobanks in Germany and England, Østergaard was able to obtain the necessary material for her study.Next steps
Østergaard's findings will be included in future research into possible chemotherapy reduction for children with B-cell ALL. Prof. Dr. Monique den Boer: 'In recent decades we have raised the cure rate to a very high level by combining medical and biological knowledge. The current therapy is super good but does take two years and gives undesirable short- and long-term side effects. It is now time to reduce therapy for those children in whom this is possible and, on the contrary, to look for alternatives for those who have an increased risk of the disease returning.'Den Boer says that in the search for these alternatives, the development of immunotherapies is essential. 'Yet even with immunotherapy, chemotherapy still remains necessary, if only to bridge the time until immunotherapy. Anna Østergaard's research teaches us that we no longer need to look at the bulk of cells, but rather at individual cells. This helps us understand why some children need only a little therapy, while others need much more therapy for the same cure rate.'
Anna Østergaard will receive her PhD from Utrecht University on Tuesday, Sept. 17. Her dissertation is entitled Towards optimal therapy for acute lymphatic leukemia in children. Her promoters and supervisors are Prof. Dr. Rob Pieters, Prof. Dr. Monique den Boer and Dr. Judith Boer.
Anna Østergaard is part of the talent program of the Princess Máxima Center Her research has been made possible thanks to funding from the Princess Máxima Center Foundation.